Variant 1-13773141-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001393986.1(PRDM2):c.575C>T(p.Thr192Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,576,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PRDM2
NM_001393986.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

PRDM2 (HGNC:9347): (PR/SET domain 2) This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

PRDM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04996997).

BS2

High AC in GnomAd at 39 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM2	NM_001393986.1 linkuse as main transcript	c.575C>T	p.Thr192Ile	missense_variant	7/10	ENST00000311066.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM2	ENST00000311066.10 linkuse as main transcript	c.575C>T	p.Thr192Ile	missense_variant	7/10	5	NM_001393986.1	P1	Q13029-1

Frequencies

GnomAD3 genomes

AF:

0.000257

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000172

AC:

AN:

214674

Hom.:

AF XY:

0.000164

AC XY:

AN XY:

115628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000555

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.000573

GnomAD4 exome

AF:

0.000106

AC:

151

AN:

1424116

Hom.:

Cov.:

AF XY:

0.0000948

AC XY:

AN XY:

706430

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000793

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000811

Gnomad4 OTH exome

AF:

0.000340

GnomAD4 genome

AF:

0.000257

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.000563

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.575C>T (p.T192I) alteration is located in exon 7 (coding exon 6) of the PRDM2 gene. This alteration results from a C to T substitution at nucleotide position 575, causing the threonine (T) at amino acid position 192 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.057

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D;D;D;D;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.13

Sift

Benign

0.033

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.94

P;P

Vest4

0.34

MVP

0.59

MPC

0.58

ClinPred

0.067

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.043

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over